Dember LM et al. (2007) Eprodisate for the treatment of renal disease in AA amyloidosis. N Engl J Med 356: 2349–2360

Deposition of fibrils in the kidneys of patients with amyloid A (AA) amyloidosis can lead to proteinuria and progressive loss of renal function. Eprodisate inhibits fibril deposition in the kidneys of mouse models of AA amyloidosis, and Dember et al. recently reported that this agent might also delay progression of AA amyloidosis-related renal dysfunction in humans.

Their multicenter double-blind trial randomized 183 patients with AA amyloidosis and kidney involvement to either eprodisate (n = 89) or placebo (n = 94) twice daily for 24 months. Disease progression was defined as a 100% increase in serum creatinine level from baseline, a decrease in creatinine clearance of at least 50%, or patient progression to end-stage renal disease or death.

In total, 124 patients (63 eprodisate and 61 placebo) completed 24 months of treatment. At the end of this period, disease was less likely to have worsened in eprodisate-treated patients than in those who received placebo (27% vs 40%; P = 0.06). Eprodisate treatment decreased the risk of worsening renal disease or death by about 40% (P = 0.02), independent of baseline renal function and changes in serum AA level. This decreased risk was a result of eprodisate's effect on the progression of kidney dysfunction (but there was no significant effect on progression to end-stage renal disease); risks of death were similar in the two groups. Creatinine clearance rate decreased significantly faster in patients in the placebo group than in eprodisate-treated patients (P = 0.02). Adverse event profiles were similar in placebo and eprodisate groups.